Epidermal growth factor strongly affects epithelial Na+ transport and barrier function in fetal alveolar cells, with minor sex-specific effects

Abstract Male sex remains an independent risk factor for respiratory distress syndrome (RDS) in preterm infants. Insufficient Na+ transport-mediated alveolar fluid clearance contributes to RDS development and we previously demonstrated sex-specific differences in Na+ transport. The epidermal growth...

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Autores principales:	Mandy Laube, Diana Dornis, Fine Wenzel, Ulrich H. Thome
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ca5dbfbcdfc24266b4edd0485176b0bb
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spelling	oai:doaj.org-article:ca5dbfbcdfc24266b4edd0485176b0bb2021-12-02T16:35:46ZEpidermal growth factor strongly affects epithelial Na+ transport and barrier function in fetal alveolar cells, with minor sex-specific effects10.1038/s41598-021-95410-y2045-2322https://doaj.org/article/ca5dbfbcdfc24266b4edd0485176b0bb2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95410-yhttps://doaj.org/toc/2045-2322Abstract Male sex remains an independent risk factor for respiratory distress syndrome (RDS) in preterm infants. Insufficient Na+ transport-mediated alveolar fluid clearance contributes to RDS development and we previously demonstrated sex-specific differences in Na+ transport. The epidermal growth factor (EGF) is important during fetal lung development with possible influence on Na+ transport. Sex-specific effects of EGF during surfactant synthesis were shown. We thus determined whether EGF exerts sex-specific effects on Na+ transport in fetal alveolar cells. We analyzed sex-specific fetal distal lung epithelial (FDLE) cells exposed to EGF and related ligands with Ussing chambers, RT-qPCR and Western blots. EGF strongly reduced the epithelial Na+ channel (ENaC) mRNA levels in both male and female FDLE cells. This was corroborated by a markedly reduced ENaC activity, while amiloride-insensitive pathways as well as barrier function were raised by EGF. In contrast to chronic effects, acute effects of EGF were sex-specific, because Na+ transport was reduced only in males. AKT phosphorylation was elevated only in female cells, while pERK1/2 was increased in both male and female cells. EGF showed certain sex- and time-dependent effects in FDLE cells. Nevertheless, the results suggest that EGF is an unlikely cause for the sex-specific differences in Na+ transport.Mandy LaubeDiana DornisFine WenzelUlrich H. ThomeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mandy Laube Diana Dornis Fine Wenzel Ulrich H. Thome Epidermal growth factor strongly affects epithelial Na+ transport and barrier function in fetal alveolar cells, with minor sex-specific effects
description	Abstract Male sex remains an independent risk factor for respiratory distress syndrome (RDS) in preterm infants. Insufficient Na+ transport-mediated alveolar fluid clearance contributes to RDS development and we previously demonstrated sex-specific differences in Na+ transport. The epidermal growth factor (EGF) is important during fetal lung development with possible influence on Na+ transport. Sex-specific effects of EGF during surfactant synthesis were shown. We thus determined whether EGF exerts sex-specific effects on Na+ transport in fetal alveolar cells. We analyzed sex-specific fetal distal lung epithelial (FDLE) cells exposed to EGF and related ligands with Ussing chambers, RT-qPCR and Western blots. EGF strongly reduced the epithelial Na+ channel (ENaC) mRNA levels in both male and female FDLE cells. This was corroborated by a markedly reduced ENaC activity, while amiloride-insensitive pathways as well as barrier function were raised by EGF. In contrast to chronic effects, acute effects of EGF were sex-specific, because Na+ transport was reduced only in males. AKT phosphorylation was elevated only in female cells, while pERK1/2 was increased in both male and female cells. EGF showed certain sex- and time-dependent effects in FDLE cells. Nevertheless, the results suggest that EGF is an unlikely cause for the sex-specific differences in Na+ transport.
format	article
author	Mandy Laube Diana Dornis Fine Wenzel Ulrich H. Thome
author_facet	Mandy Laube Diana Dornis Fine Wenzel Ulrich H. Thome
author_sort	Mandy Laube
title	Epidermal growth factor strongly affects epithelial Na+ transport and barrier function in fetal alveolar cells, with minor sex-specific effects
title_short	Epidermal growth factor strongly affects epithelial Na+ transport and barrier function in fetal alveolar cells, with minor sex-specific effects
title_full	Epidermal growth factor strongly affects epithelial Na+ transport and barrier function in fetal alveolar cells, with minor sex-specific effects
title_fullStr	Epidermal growth factor strongly affects epithelial Na+ transport and barrier function in fetal alveolar cells, with minor sex-specific effects
title_full_unstemmed	Epidermal growth factor strongly affects epithelial Na+ transport and barrier function in fetal alveolar cells, with minor sex-specific effects
title_sort	epidermal growth factor strongly affects epithelial na+ transport and barrier function in fetal alveolar cells, with minor sex-specific effects
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ca5dbfbcdfc24266b4edd0485176b0bb
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Epidermal growth factor strongly affects epithelial Na+ transport and barrier function in fetal alveolar cells, with minor sex-specific effects

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